Temporal pattern of Fos and Jun families expression after mitogenic stimulation with FGF-2 in rat neural stem cells and fibroblasts

Intense stimulation of most living cells triggers the activation of immediate early genes, such as Fos and Jun families. These genes are important in cellular and biochemical processes, such as mitosis and cell death. The present study focused on determining the temporal expression pattern of Fos and Jun families in fibroblasts and neural stem cells of cerebellum, hippocampus, and subventricular zone (SVZ) of rats of different ages at 0, 0.5, 1, 3, and 6 h after stimulation with fibroblast growth factor (FGF)-2. In neonates, a similar expression pattern was observed in all cells analyzed, with lower expression in basal condition, peak expression at 0.5 h after stimulation, returning to baseline values between 1 and 3 h after stimulation. On the other hand, cells from adult animals only showed Fra1 and JunD expression after stimulation. In fibroblasts and hippocampus, Fra1 reached peak expression at 0.5 h after stimulation, while in the SVZ, peak level was observed at 6 h after stimulation. JunD in fibroblasts presented two peak expressions, at 0.5 and 6 h after stimulation. Between these periods, the expression observed was at a basal level. Nevertheless, JunD expression in SVZ and hippocampus was low and without significant changes after stimulation. Differences in mRNA expression in neonate and adult animals characterize the significant differences in neurogenesis and cell response to stimulation at different stages of development. Characterizing these differences might be important for the development of cell cultures, replacement therapy, and the understanding of the physiological response profile of different cell types.

Immediate expression of c-fos and c-jun mRNA in a model of intestinal autotransplantation and ischemia-reperfusion in situ

OBJECTIVE: Intestinal ischemia-reperfusion injury occurs in several clinical conditions and after intestinal transplantation. The aim of the present study was to investigate the phenomena of apoptosis and cell proliferation in a previously described intestinal ischemia-reperfusion injury autograft model using immunohistochemical markers. The molecular mechanisms involved in ischemia-reperfusion injury repair were also investigated by measuring the expression of the early activation genes c-fos and c-jun, which induce apoptosis and cell proliferation. MATERIALS AND METHODS: Thirty adult male Wistar rats were subjected to surgery for a previously described ischemia-reperfusion model that preserved the small intestine, the cecum and the ascending colon. Following reperfusion, the cecum was harvested at different time points as a representative segment of the intestine. The rats were allocated to the following four subgroups according to the reperfusion time: subgroup 1: 5 min; subgroup 2: 15 min; subgroup 3: 30 min; and subgroup 4: 60 min. A control group of cecum samples was also collected. The expression of c-fos, c-jun and immunohistochemical markers of cell proliferation and apoptosis (Ki67 and TUNEL, respectively) was studied. RESULTS: The expression of both c-fos and c-jun in the cecum was increased beginning at 5 min after ischemia-reperfusion compared with the control. The expression of c-fos began to increase at 5 min, peaked at 30 min, and exhibited a declining tendency at 60 min after reperfusion. A progressive increase in c-jun expression was observed. Immunohistochemical analyses confirmed these observations. CONCLUSION: The early activation of the c-fos and c-jun genes occurred after intestinal ischemia-reperfusion injury, and these genes can act together to trigger cell proliferation and apoptosis. .

A study on the mechanism of traumatic brain injury affecting the speed of bone fracture healing / 中华急诊医学杂志

Objective To evaluate the possible mechanism of traumatic brain injury (TB1) affecting the speed of bone fracture healing.Method TBI combined with unilateral tibial fracture (group A) was used to build multiple injury model and simple unilateral tibial fracture (group B),and the FOS,JUN,bFGF,and VEGF protein expression in different time points between the two groups were compared,and roentgenogram was used for the evaluation of bone healing.Results The expression of FOS,JUN,bFGF,and VEGF protein of the cerebral tissue was low in the normal rats,but was slightly enhanced in group B.There was consistence of development for FOS and JUN expression in the brain tissue in group A,reaching peak at post-TBI 3 hours,and then reducing to control level after 12 hours.The bFGF and VEGF reached peak at post-TBI 12 hours and 24 hours and reduced to control level after 72 hours,respectively.In group A and group B,an increase in the FOS,JUN protein expression around the fracture site was observed at 3 hours after injury,which reached the peak at 6 hours,and reduced to the control level after 24 hours;the comparison between group A,group B and the control group at 3 hours,6 hours and 12 hours had significant difference (P

Effects of heavy metals on mitogen-activated protein kinase pathways

The signaling pathways leading to cellular protection or cell death following exposure to heavy metals have not been fully clarified. Mitogen-activated protein kinases (MAPKs), i.e., extracellular signal-regulated protein kinase (ERK), c-Jun NH(2)-terminal kinase (JNK) and p38 MAPK transmit extracellular signals into the nucleus, and have been shown to participate in a diverse array of cellular functions such as cell growth, differentiation and apoptosis. Treatment with cadmium, inorganic mercury or tributyltin can activate ERK, JNK and p38 MAPK, and induces the expression of c-fos and c-jun genes prior to the development of apoptosis. However, the members of the MAPK family appear to be differentially activated depending on the heavy metal and the cell type exposed. Consequently, various cellular responses may be caused by the distinct pattern of MAPKs activation. MAPKs may be one of the important cellular signal transduction pathways affected by various environmental pollutants, including heavy metals.

Effects of Heavy Metals on Mitogen-Activated Protein Kinase Pathways

The signaling pathways leading to cellular protection or cell death following exposure to heavy metals have not been fully clarified. Mitogen-activated protein kinases (MAPKs), i.e., extracellular signal-regulated protein kinase (ERK), c-Jun NH2-terminal kinase (JNK) and p38 MAPK transmit extracellular signals into the nucleus, and have been shown to participate in a diverse array of cellular functions such as cell growth, differentiation and apoptosis. Treatment with cadmium, inorganic mercury or tributyltin can activate ERK, JNK and p38 MAPK, and induces the expression of c-fos and c-jun genes prior to the development of apoptosis. However, the members of the MAPK family appear to be differentially activated depending on the heavy metal and the cell type exposed. Consequently, various cellular responses may be caused by the distinct pattern of MAPKs activation. MAPKs may be one of the important cellular signal transduction pathways affected by various environmental pollutants, including heavy metals.

A study on the expression of immediate-early genes by light stimuli in the rat suprachiasmatic nucleus using differential display / 대한해부학회지

The hypothalamic suprachiasmatic nucleus (SCN) of the mammal is the circadian pacemaker responsible for generation of circadian rhythms. Several immediate-early genes are expressed in the SCN by light stimuli which induce phase shifts of animal activity rhythms. By using differential display-polymerase chain reaction, we investigated expression of several immediate-early genes in the light-stimulated SCN. In addition, we analyzed the light-induced expression changes of two known immediate-early genes, Arc and Rheb, in the SCN. We have screened and cloned 25 differentially expressed genes in the SCN, and identified a gene, a rat homologue of A6 kinase, which expression was regulated by light stimuli. One hour light stimuli during the subjective night dramatically induced the gene expression in the SCN, whereas light stimuli during the subjective light phase did not. This finding implies that a rat homolgue of A6 kinase may be involved in the photic entrainment of the circadian clock. On the other hand, Arc and Rheb mRNA expressions were not increased in the SCN by light stimuli.

Expression of Immediate Early Genes Messenger RNAs in Focally Ischemic Rat Brain Following Delayed Postischemic Hyperthermia

Previous studies have indicated that hyperthermic modulation in the delayed postischemic period, even when occurring days after an ischemic insult, may augment ischemic injury. In order to evaluate the molecular mechanisms of the detrimental effects of hyperthermia on ischemic outcome, we performed a study to assess the effects of delayed postischemic hyperthermia on the regional expression of message for the immediate early genes c-fos and c-jun. 60 minutes of transient middle cerebral artery occlusion was produced in rats by insertion of an intraluminal filament. 24 hours after reperfusion, rats which were awake were subjected to normothermic(37-38degreesC) or hyperthermic(40degreesC) temperature modulation for 3 hours in a heating chamber. Either 2 or 24 hours after temperature modulation, brains were examined for mRNA expression of c-fos and c-jun by the dot blot method. Four regions of interest were chosen: fronto-cingulate, sensorimotor, piriform-insular cortex, and caudoputamen. Dot blot analysis revealed that c-fos mRNA at 2 hours after temperature modulation was significantly upregulated in the ipsilateral fronto-cingulate cortex-the site of the ischemic penumbra- in rats exposed to ischemia+delayed hyperthermia, in comparison to rats exposed to sham+normothermia(one-way ANOVA with post-hoc Bonferroni's test, p<0.05). In contrast, c-jun mRNA was significantly upregulated by ischemia+delayed hyperthermia within regions of core ischemia-i.e., sensorimotor and piriform-insular cortex, and caudoputamen. These findings have extended those of our earlier histopathological study10) to show that a significant increase in c-fos or c-jun expression may be closely linked to cellular survival or death after delayed moderate hyperthermia following ischemia.